Cytomegalovirus (CMV) continues to exert a significant detrimental impact upon patient and allograft survival after solid organ transplantation. Our ongoing studies clearly demonstrate the need for improved intervention to limit the adverse effects of CMV. We propose to conduct a randomized clinical trial in which the most efficacious means of reducing the impact of CMV infection and disease upon patient and allograft survival is examined at two levels of intervention: 1) prophylaxis, and 2) treatment in solid organ transplant recipients; and to intensively examine the pathogenesis of CMV infection and disease via analysis of the results of both immunologic and molecular assays with specific emphasis upon 1) viral detection, dissemination, and drug resistance, and 2) viral latency and transmission in this patient population. These studies will be tightly integrated in order to provide a great deal of information concerning the epidemiology of CMV and the effects of anti-viral agent intervention upon clinical parameters that will be directly linked with an examination of the pathogenesis of CMV infection and disease with regard to virologic, immunologic, and molecular biologic parameters. These studies should provide a great deal of insight into the pathogenesis of CMV disease and should serve to facilitate the implementation of subsequent clinical interventional trials.